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Temozolomide and Radiation Therapy in Treating Patients With Newly Diagnosed Glioblastoma Multiforme or Anaplastic Astrocytoma

Primary Purpose

Glioblastoma Multiforme/Anaplastic Astrocytoma

Status
Completed
Phase
Phase 1
Locations
United States
Study Type
Interventional
Intervention
temozolomide
Hypofractionated radiation therapy
Intensity-modulated radiation therapy
Sponsored by
Ohio State University Comprehensive Cancer Center
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Glioblastoma Multiforme/Anaplastic Astrocytoma focused on measuring adult giant cell glioblastoma, adult gliosarcoma, adult anaplastic astrocytoma, adult glioblastoma, GBM/AA

Eligibility Criteria

18 Years - undefined (Adult, Older Adult)All SexesDoes not accept healthy volunteers

Inclusion Criteria:

  • Patients who have De novo glioblastoma multiforme, anaplastic astrocytoma, anaplastic oligodendrogliomas, mixed anaplastic oligoastrocytomas, gliosarcoma of the Brain, not involving the brain stem or optics chiasm, diagnosed following biopsy or tumor removal.
  • Age > 18 years
  • Given written consent
  • Adequate bone marrow reserve(hemoglobin > 10 grams, Absolute neutrophil count > 1500 / mm3, platelets > 100,000/ mm3)
  • Normal renal function(BUN < 24 mg/dL, Creatinine < 1.3 mg/dL)
  • Normal liver function(Total Bilirubin < 1.5 mg/dL, SGPT/ALT < 60 U/L)

Exclusion Criteria:

  • Have a Karnofsky score of < 60 [Appendix B] or age < 18 years.
  • Prior chemotherapy and/or radiotherapy of their glioblastomamultiforme, anaplastic astrocytoma, anaplastic oligodendrogliomas, mixed anaplastic oligoastrocytomas, gliosarcoma.
  • Tumors located in the brainstem or optic chiasm.
  • Prior radiation therapy to the brain
  • Prior chemotherapy within the past 6 weeks.

Sites / Locations

  • Ohio State University Comprehensive Cancer Center

Arms of the Study

Arm 1

Arm Type

Experimental

Arm Label

Hypofractionation Radiotherapy+Temozolomide

Arm Description

Patients will receive temozolomide PO daily for 5 weeks. Beginning week 1 after initiation of temozolomide therapy, patients undergo HIMRT times a week for a total of 15 fractions.

Outcomes

Primary Outcome Measures

Maximum Tolerated Dose(MTD)of Temozolomide(TMZ)
This study is designed as a phase I dose escalation trial using the Standard Method of dose escalation of three patients per dose level to determine the MTD of TMZ (up to 75 mg/m 2 /day) when TMZ is used with HIMRT for patients with glioblastoma multiforme(GBM) or Anaplastic Astrocytoma(AA)of the brain. The 3 dose levels will be evaluated using the standard method to determine if either represents an MTD based on DLT. If DLT is not observed at all doses level, the greater of the three levels will be recommended for phase II evaluations of treatment effect.

Secondary Outcome Measures

Time to Neuroradiological Evidence of Tumor Recurrence or Progression
As a small phase I study, no inferential statistical tests of hypotheses are planned. Data collected will be providing descriptive summary statistics. However, these estimates will allow statistically sound experimental designs and sample size calculations for subsequent studies of therapeutic effect.
Survival Time
All patients will be followed to death. Active follow-up with disease evaluation with scans will be terminated if the patient's physician deems it in the patient's interest not to continue or upon patient request.
Time Spent in a Karnofsky Performance Status of 60-100%
Time spent in a KPS ≥70 was calculated from the date of diagnosis of Karonofsky Performance Status decline (KPS<70) or censored at the last date the patient was known with KPS ≥70. The KPS higher scores indicates normal activity status.

Full Information

First Posted
February 10, 2009
Last Updated
April 16, 2018
Sponsor
Ohio State University Comprehensive Cancer Center
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1. Study Identification

Unique Protocol Identification Number
NCT00841555
Brief Title
Temozolomide and Radiation Therapy in Treating Patients With Newly Diagnosed Glioblastoma Multiforme or Anaplastic Astrocytoma
Official Title
A Phase I Trial of Hypofraction Radiotherapy + Temozolomide in the Treatment of Patients With Glioblastoma Multiforme and Anaplastic Astrocytoma of the Brain
Study Type
Interventional

2. Study Status

Record Verification Date
April 2018
Overall Recruitment Status
Completed
Study Start Date
February 13, 2009 (Actual)
Primary Completion Date
February 13, 2013 (Actual)
Study Completion Date
November 25, 2014 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Ohio State University Comprehensive Cancer Center

4. Oversight

Data Monitoring Committee
Yes

5. Study Description

Brief Summary
RATIONALE: Drugs used in chemotherapy, such as temozolomide, work in different ways to stop the growth of tumor cells, either by killing the cells or by stopping them from dividing. Radiation therapy uses high-energy x-rays to kill tumor cells. Specialized radiation therapy that delivers a high dose of radiation directly to the tumor may kill more tumor cells and cause less damage to normal tissue. Giving chemotherapy together with radiation therapy may kill more tumor cells. PURPOSE: This phase I trial is studying the side effects and best dose of temozolomide when given together with radiation therapy in treating patients with newly diagnosed glioblastoma multiforme or anaplastic astrocytoma.
Detailed Description
OBJECTIVES: Primary To determine the maximum tolerated dose of temozolomide when given in combination with hypofractionated intensity-modulated conformal stereotactic radiotherapy in patients with newly diagnosed de novo glioblastoma multiforme or anaplastic astrocytoma. Secondary To determine the time to neuroradiological evidence of tumor recurrence or progression in patients treated with this regimen. To determine the survival time of patients treated with this regimen. To determine the time spent in a Karnofsky performance status of 60-100%. OUTLINE: This is a dose-escalation study of temozolomide. Beginning 1-3 weeks following surgery or biopsy, patients receive oral temozolomide once daily for 5 weeks. Beginning 1 week after starting temozolomide, patients also undergo hypofractionated intensity-modulated conformal stereotactic radiotherapy once daily 5 days a week for 3 weeks. After completion of study treatment, patients are followed at 1 month, 2 months, and 3 months, and then every 3 months thereafter.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Glioblastoma Multiforme/Anaplastic Astrocytoma
Keywords
adult giant cell glioblastoma, adult gliosarcoma, adult anaplastic astrocytoma, adult glioblastoma, GBM/AA

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 1
Interventional Study Model
Single Group Assignment
Masking
None (Open Label)
Allocation
N/A
Enrollment
9 (Actual)

8. Arms, Groups, and Interventions

Arm Title
Hypofractionation Radiotherapy+Temozolomide
Arm Type
Experimental
Arm Description
Patients will receive temozolomide PO daily for 5 weeks. Beginning week 1 after initiation of temozolomide therapy, patients undergo HIMRT times a week for a total of 15 fractions.
Intervention Type
Drug
Intervention Name(s)
temozolomide
Other Intervention Name(s)
Temodar, Temodal
Intervention Description
Chemotherapy will be given for 5 weeks; it will start 1 week before Radiotherapy, will continue for the 3 weeks of Radiotherapy, and will continue for 1 week post-Radiotherapy. Dose Level 1: 50 mg/m2 x first 4 weeks/75 mg/m2 x last 1 weeks of treatment Dose Level 2: 65 mg/m2 x first 4 weeks/75 mg/m2 x last 1 weeks of treatment Dose Level 3: 75 mg/m2 over the entire 5 weeks of treatment
Intervention Type
Radiation
Intervention Name(s)
Hypofractionated radiation therapy
Intervention Description
Patients will undergo HIMRT
Intervention Type
Radiation
Intervention Name(s)
Intensity-modulated radiation therapy
Other Intervention Name(s)
IMRT
Intervention Description
Patients undergo HIMRT
Primary Outcome Measure Information:
Title
Maximum Tolerated Dose(MTD)of Temozolomide(TMZ)
Description
This study is designed as a phase I dose escalation trial using the Standard Method of dose escalation of three patients per dose level to determine the MTD of TMZ (up to 75 mg/m 2 /day) when TMZ is used with HIMRT for patients with glioblastoma multiforme(GBM) or Anaplastic Astrocytoma(AA)of the brain. The 3 dose levels will be evaluated using the standard method to determine if either represents an MTD based on DLT. If DLT is not observed at all doses level, the greater of the three levels will be recommended for phase II evaluations of treatment effect.
Time Frame
up to 12-16 months
Secondary Outcome Measure Information:
Title
Time to Neuroradiological Evidence of Tumor Recurrence or Progression
Description
As a small phase I study, no inferential statistical tests of hypotheses are planned. Data collected will be providing descriptive summary statistics. However, these estimates will allow statistically sound experimental designs and sample size calculations for subsequent studies of therapeutic effect.
Time Frame
up to 12-16 months
Title
Survival Time
Description
All patients will be followed to death. Active follow-up with disease evaluation with scans will be terminated if the patient's physician deems it in the patient's interest not to continue or upon patient request.
Time Frame
up to 2 years
Title
Time Spent in a Karnofsky Performance Status of 60-100%
Description
Time spent in a KPS ≥70 was calculated from the date of diagnosis of Karonofsky Performance Status decline (KPS<70) or censored at the last date the patient was known with KPS ≥70. The KPS higher scores indicates normal activity status.
Time Frame
up to 12-16 months

10. Eligibility

Sex
All
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria: Patients who have De novo glioblastoma multiforme, anaplastic astrocytoma, anaplastic oligodendrogliomas, mixed anaplastic oligoastrocytomas, gliosarcoma of the Brain, not involving the brain stem or optics chiasm, diagnosed following biopsy or tumor removal. Age > 18 years Given written consent Adequate bone marrow reserve(hemoglobin > 10 grams, Absolute neutrophil count > 1500 / mm3, platelets > 100,000/ mm3) Normal renal function(BUN < 24 mg/dL, Creatinine < 1.3 mg/dL) Normal liver function(Total Bilirubin < 1.5 mg/dL, SGPT/ALT < 60 U/L) Exclusion Criteria: Have a Karnofsky score of < 60 [Appendix B] or age < 18 years. Prior chemotherapy and/or radiotherapy of their glioblastomamultiforme, anaplastic astrocytoma, anaplastic oligodendrogliomas, mixed anaplastic oligoastrocytomas, gliosarcoma. Tumors located in the brainstem or optic chiasm. Prior radiation therapy to the brain Prior chemotherapy within the past 6 weeks.
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Mario Ammirati, MD
Organizational Affiliation
Ohio State University Comprehensive Cancer Center
Official's Role
Principal Investigator
Facility Information:
Facility Name
Ohio State University Comprehensive Cancer Center
City
Columbus
State/Province
Ohio
ZIP/Postal Code
43210
Country
United States

12. IPD Sharing Statement

Citations:
PubMed Identifier
24380758
Citation
Ammirati M, Chotai S, Newton H, Lamki T, Wei L, Grecula J. Hypofractionated intensity modulated radiotherapy with temozolomide in newly diagnosed glioblastoma multiforme. J Clin Neurosci. 2014 Apr;21(4):633-7. doi: 10.1016/j.jocn.2013.09.005. Epub 2013 Oct 3.
Results Reference
result
Links:
URL
http://cancer.osu.edu
Description
Jamesline

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Temozolomide and Radiation Therapy in Treating Patients With Newly Diagnosed Glioblastoma Multiforme or Anaplastic Astrocytoma

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